BLU-945
(Synonyms: 蓝-945) 目录号 : GC63910
BLU-945是一种高效、高选择性、可逆且具有口服活性的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）。
Cas No.:2660250-10-0
Sample solution is provided at 25 µL, 10mM.
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BLU-945 is a potent, highly selective, reversible and orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)[1]. EGFR plays a crucial role in cell proliferation, differentiation, survival, and migration, and its gene mutations are one of the key drivers of non-small cell lung cancer (NSCLC)[2]. BLU-945 can effectively inhibit EGFR with L858R and/or exon 19 deletion mutation, T790M mutation and C797S mutation[3]. The IC50 value of BLU-945 for EGFR L858R/C797S is 28.9nM, and for EGFR ex19del/C797S is 108.8nM[3]. BLU-945 is usually used for the research of lung cancer including non-small cell lung cancer (NSCLC)[4-7].
In vitro，BLU-945 (0-10mM; 4h) inhibited EGFR phosphorylation in cell lines harboring EGFR L858R/T790M/C797S and EGFR ex19del/T790M/C797S mutations and inhibited cell viability and growth of EGFR mutant/osimertinib-resistant cell lines[3].
In vivo, in osimertinib-resistant models of NSCLC (osimertinib second line: EGFR_L858R/C797S and third line: EGFR_ex19del/T790M/C797S and L858R/T790M/C797S), treatment of BLU-945(orally; 100mg/kg; bid; 30d) alone or combinated with osimertinib demonstrated tumor shrinkage and inhibition of the EGFR pathway[3].
References:
[1] John Emmerson Campbell, et al. Inhibitors of mutant forms of egfr. Patent WO2021133809A1.
[2] Melosky, B., Kambartel, K., Häntschel, M., Bennetts, M., Nickens, D. J., Brinkmann, J., Kayser, A., Moran, M., & Cappuzzo, F. (2022). Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis. Molecular diagnosis & therapy, 26(1), 7–18.
[3] Lim, S. M., Schalm, S. S., Lee, E. J., Park, S., Conti, C., Millet, Y. A., Woessner, R., Zhang, Z., Tavera-Mendoza, L. E., Stevison, F., Albayya, F., Dineen, T. A., Hsieh, J., Oh, S. Y., Zalutskaya, A., Rotow, J., Goto, K., Lee, D. H., Yun, M. R., & Cho, B. C. (2024). BLU-945, a potent and selective next-generation EGFR TKI, has antitumor activity in models of osimertinib-resistant non-small-cell lung cancer. Therapeutic advances in medical oncology, 16, 17588359241280689.
[4] Eno, M. S., Brubaker, J. D., Campbell, J. E., De Savi, C., Guzi, T. J., Williams, B. D., Wilson, D., Wilson, K., Brooijmans, N., Kim, J., Özen, A., Perola, E., Hsieh, J., Brown, V., Fetalvero, K., Garner, A., Zhang, Z., Stevison, F., Woessner, R., Singh, J., … Dineen, T. A. (2022). Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer. Journal of medicinal chemistry, 65(14), 9662–9677.
[5] Kannan, K., & Mohan, S. (2025). Targeting exon mutations in NSCLC: clinical insights into LAG-3, TIM-3 pathways, and advances in fourth-generation EGFR-TKIs. Medical oncology (Northwood, London, England), 42(6), 196.
[6] Shum E, Elamin Y, Piotrowska Z, Spigel DR, Reckamp KL, Rotow J, et al.(2022). EP08.02–045 phase 1/2 study of BLU-945 in patients with common activating EGFR-mutant non-small cell lung cancer. Journal of Thoracic Oncology. 2022;17(9):S418.
[7] Elamin Y, Nagasaka M, Shum E, Bazhenova L, Camidge D, Cho B, et al. BLU-945 monotherapy and in combination with osimertinib (OSI) in previously treated patients with advanced EGFR -mutant (EGFRm) NSCLC in the phase 1/2 SYMPHONY study. J Clin Oncol. 2023;41:9011–9011.
BLU-945是一种高效、高选择性、可逆且具有口服活性的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）[1]。EGFR在细胞增殖、分化、存活和迁移等多种生物学过程中发挥关键作用，其基因突变是非小细胞肺癌（NSCLC）的重要驱动因素之一[2]。BLU-945能够有效抑制EGFR的L858R和/或外显子19缺失突变、T790M突变以及C797S突变[3]。BLU-945对EGFR L858R/C797S的IC50值为28.9nM，对EGFR ex19del/C797S的IC50值为108.8nM[3]。BLU-945通常用于非小细胞肺癌（NSCLC）等肺癌研究[4-7]。
体外实验中，BLU-945（0-10mM；4小时）抑制了携带EGFR L858R/T790M/C797S和EGFR ex19del/T790M/C797S突变的细胞系中EGFR的磷酸化，并抑制了EGFR突变/奥希替尼耐药细胞系的细胞活性和生长[3]。
体内实验中，在奥希替尼耐药的NSCLC模型中（奥希替尼二线治疗：EGFR L858R/C797S；奥希替尼三线治疗：EGFR ex19del/T790M/C797S和L858R/T790M/C797S），无论是单药治疗还是与奥希替尼联合使用，BLU-945（口服；100 mg/kg；每日两次；30天）均显示出肿瘤缩小和EGFR信号通路的抑制[3]。
| Cell experiment [1]: | |
Cell lines | Ba/F3 cells, PC9, PC9_DC, YU-1182, and YU-1097 |
Preparation Method | Cells were seeded and incubated for 3 days for Ba/F3 cells, PC9, PC9_DC, YU-1182, and YU-1097. Cells were treated with BLU-945, osimertinib, or gefitinib at 10 different concentrations ranging from 0.095 to 25,000nM. 0.1% dimethyl sulfoxide (DMSO) and 25,000nM staurosporine were used as negative and positive controls, respectively. After 4h of treatment, cells were processed using the PhosphoEGFR (Tyr1068) AlphaLISA SureFire Ultra Detection Kit according to the manufacturer’s instructions. Viability was measured using CellTiter-Glo® assay. |
Reaction Conditions | 0.095 to 25,000nM; 4h |
Applications | BLU-945 inhibited EGFR phosphorylation,cell viability and growth. |
| Animal experiment [1]: | |
Animal models | Female nu/nu mice; female NOD-SCID mice |
Preparation Method | To generate YU-1097 PDCderived tumor xenograft models, cells (5 × 106 in 100µL) were implanted subcutaneously into the flanks of 6-week-old female nu/nu mice. To generate an EGFR_L858R/C797S-expressing Ba/F3 syngeneic injection model, cells (3 × 106 in 200µL) were implanted into the flank of female NOD-SCID mice. Prior to the onset of drug treatment, mice were measured for tumor size in two dimensions and the tumor volume (mm3) was calculated using formula V=0.5 a×b2 where a and b are the long and short diameters of the tumor in mm, respectively. Mice were randomly grouped when the tumor volume reached 200mm3 and allocated to the following treatment groups: vehicle, osimertinib (25mg/kg once daily [QD]), BLU-945 (100mg/kg twice daily [BID]), and combinations of osimertinib with BLU-945. BLU-945 and osimertinib were formulated in 20% Solutol HS 15 with 0.5% methylcellulose and dosed orally for 30 days. Tumor size and body weight were measured twice weekly. Tumor samples were harvested and snap-frozen for subsequent analysis. |
Dosage form | 100mg/kg/day for 30 days; bid; p.o. |
Applications | Treatment of BLU-945 demonstrated tumor shrinkage and inhibition of the EGFR pathway both as monotherapy and in combination with osimertinib. |
References: | |
| Cas No. | 2660250-10-0 | SDF | Download SDF |
| 别名 | 蓝-945 | ||
| 分子式 | C28H37FN6O3S | 分子量 | 556.7 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7963 mL | 8.9815 mL | 17.963 mL |
| 5 mM | 0.3593 mL | 1.7963 mL | 3.5926 mL |
| 10 mM | 0.1796 mL | 0.8981 mL | 1.7963 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
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